Final results of the IFCT-0803 study, a phase II study of cetuximab, pemetrexed, cisplatin, and concurrent radiotherapy in patients with locally advanced, unresectable, stage III, non-squamous, non-small-cell lung cancer.

PURPOSE: Roughly 20% of patients with non-small-cell lung cancer exhibit locally advanced, unresectable, stage III disease. Concurrent platinum-based chemoradiotherapy is the backbone treatment, which is followed by maintenance immunotherapy, yet with poor long-term prognosis. This phase II trial (IFCT-0803) sought to evaluate whether adding cetuximab to cisplatin and pemetrexed chemoradiotherapy would improve its efficacy in these patients. MATERIALS AND METHODS: Eligible patients received weekly cetuximab (loading dose 400mg/m2 day 1; subsequent weekly 250mg/m2 doses until two weeks postradiotherapy). Chemotherapy comprised cisplatin (75mg/m2) and pemetrexed (500mg/m2), both delivered on day 1 of a 21-day cycle of maximally four. Irradiation with maximally 66Gy started on day 22. Disease control rate at week 16 was the primary endpoint. RESULTS: One hundred and six patients were included (99 eligible patients). Compliance exceeded 95% for day 1 of chemotherapy cycles 1 to 4, with 76% patients receiving the 12 planned cetuximab doses. Maximal grade 3 toxicity occurred in 63% patients, and maximal grade 4 in 9.6%. The primary endpoint involving the first 95 eligible patients comprised two (2.1%) complete responses, 57 (60.0%) partial responses, and 27 (28.4%) stable diseases. This 90.5% disease control rate (95% confidence interval [95% CI]: 84.6%-96.4%) was achieved at week 16. After median 63.0-month follow-up, one-year and two-year survival rates were 75.8% and 59.5%. Median overall survival was 35.8months (95% CI: 23.5-NR), and median progression-free survival 14.4months (95% CI: 11.2-18.8), with one-year and two-year progression-free survival rates of 57.6% and 34.3%. CONCLUSION: These survival rates compare favourably with published data, thus justifying further development of cetuximab-based induction chemoradiotherapy.

Real world data of efficacy and safety of erlotinib as first-line TKI treatment in EGFR mutation-positive advanced non-small cell lung cancer: Results from the EGFR-2013-CPHG study.

BACKGROUND: Phase III clinical trials have demonstrated the merits of epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKI) in the treatment of non-small cell lung cancer (NSCLC) patients with EGFR-activating mutations. Using a cohort of unselected patients treated with erlotinib, we sought to further describe patient and tumour characteristics, and to evaluate their progression-free survival (PFS) and overall survival (OS). METHODS: Overall, 44 pulmonologists included patients with the required characteristics as follows: Stage IIIB-IV NSCLC, EGFR-activating mutation, age≥18 years, and having to start erlotinib therapy or receiving erlotinib therapy as the first-line TKI, regardless of treatment-line. The analyses were performed using R software, with survival rates calculated according to the Kaplan-Meier method. RESULTS: A total of 177 patients, aged 72 years on average, were enrolled over a 2-year period. The cohort included 123 women (69.5%), 158 Caucasians (89.3%), 112 non-smokers (63.2%), and 167 adenocarcinomas (94.3%), at either stage IIIB (21) or IV (156), with a good performance status (PS 0-1, 127). Overall, 40 exhibited brain metastases at baseline (22.6%), while 75 had undergone earlier treatment (42.4%). Median PFS was 11.7 months and OS 25.8 months, with respectively a 1-year rate of 48.6% and 74%. The risk of death correlated with ECOG status (PS=2, HR=4.48, P<0.001) but not with brain metastasis (HR=1.67, P=0.278). CONCLUSIONS: This study has confirmed erlotinib's efficacy and safety for unselected patients, with PFS and OS comparable to those obtained in phase III trials.

Oral manifestations of celiac disease in French children.

Celiac disease (CD) is an immune-mediated systemic disorder caused by ingestion of the gluten found in wheat, rye, and barley. The currently estimated prevalence in children is about 1%. CD is a chronic enteropathy with gastrointestinal manifestations including diarrhea, abdominal distension and weight loss, but extra-intestinal features are increasingly being reported. Dental and oral manifestations such as dental enamel defects (ED), delay in dental eruption, and recurrent aphthous stomatitis (RAS) are well-recognized manifestations of CD. The aim of this study was to compare the frequency of oral manifestations (ED, RAS and delay in dental eruption) on deciduous and permanent teeth between children with CD and a control population. An oral examination was performed on 28 CD children and 59 control children. All children were younger than 12 years old and had deciduous or mixed dentition. CD children had significantly more ED and RAS than the control group (67.9% vs. 33.9% P=0.004 and 50.0% vs. 21.8% P=0.011, respectively). No delay in dental eruption was observed in CD children. ED were mainly grade I and II of Aine's classification (color defects and slight structural defects). ED were more often seen on CD children's deciduous teeth than on permanent teeth (57.1% and 13.6%, respectively; P<0.001). The main teeth affected by ED are the second molar and canines of the deciduous teeth, and the first molar, central incisor, and lateral incisors of the permanent teeth. RAS and ED that were symmetrical in all quadrants and occurred firstly in teeth that mineralize during the first year of life both seem to be signs of CD. Thus, more information for dentists and pediatricians on these oral manifestations should help improve detection of CD.

PREMIUM: A French prospective multicenter observational study of factors impacting on efficacy and compliance to cetuximab treatment in first-line KRAS wild-type metastatic colorectal cancer.

BACKGROUND: Cetuximab improves progression-free survival (PFS) and overall survival (OS) in patients with KRAS wild type (wt) metastatic colorectal cancer (mCRC). Few data are available on factors impacting both efficacy and compliance to cetuximab treatment, which is, in combination with chemotherapy, a standard-of-care first-line treatment regimen for patients with KRAS wt mCRC. PATIENTS AND METHODS: PREMIUM is a prospective, French multicenter, observational study that recruited patients with KRAS wt mCRC scheduled to receive cetuximab, with or without first-line chemotherapy, as part of routine clinical practice, between October 28, 2009 and April 5, 2012 (ClinicalTrials.gov Identifier: NCT01756625). The main endpoints were the factors impacting on efficacy and compliance to cetuximab treatment. Predefined efficacy endpoints were PFS and safety. RESULTS: A total of 493 patients were recruited by 94 physicians. Median follow-up was 12.9 months. Median progression-free survival was 11 months [9.6-12]. In univariate analyses, ECOG performance status (PS), smoking status, primary tumor location, number of metastatic organs, metastasis resectability, surgery, folliculitis, xerosis and paronychia maximum grade, and acne preventive treatment were statistically significant. In multivariate analysis (Hazard Ratios of multivariate stepwise Cox models), ECOG PS, surgery, xerosis and folliculitis were positive prognostics factors for longer PFS. Among all patients, 69 (14%) were non-compliant. In multivariate analysis, no variables were statistically significant. The safety profile of cetuximab was consistent with previous studies. CONCLUSIONS: ECOG PS <2, surgical treatment performed, and maximum grade xerosis or folliculitis developed were predictive factors of cetuximab efficacy on KRAS wt mCRC patients. Unfortunately, we failed in identifying predictive factors for compliance in these patients.

Revisiting hybrid breeding designs using genomic predictions: simulations highlight the superiority of incomplete factorials between segregating families over topcross designs.

KEY MESSAGE: Simulations showed that hybrid performances issued from an incomplete factorial between segregating families of two heterotic groups enable to calibrate genomic predictions of hybrid value more efficiently than tester-based designs. Genomic selection offers new opportunities to revisit hybrid breeding by replacing extensive phenotyping of hybrid combinations by genomic predictions. A key question remains to identify the best design to calibrate genomic prediction models. We proposed to use single-cross hybrids issued from an incomplete factorial design between segregating populations and compared this strategy with a conventional approach based on topcross evaluation. Two multiparental segregating populations of lines, each specific of one heterotic group, were simulated. Hybrids considered as training sets were generated using either (1) a parental line from the opposite group as tester or (2) following an incomplete factorial design. Different specific combining ability (SCA) proportions were simulated by considering different levels of group divergence and dominance effects for the simulated QTL. For the incomplete factorial design, for a same number of hybrids, we considered different numbers of parental lines and different contributions of lines (one to four) to calibration hybrids. We evaluated for different training set sizes prediction accuracies of new hybrids and genetic gains along three generations. At a given training set size, factorial design was as efficient (considering accuracy) as tester design in additive scenarios, but significantly outperformed tester design when SCA was present. The contribution number of each parental line to the incomplete factorial design had a small impact on accuracies. Our simulations confirmed experimental results and showed that calibrating models on hybrids between two multiparental populations is a cost-efficient way to perform genomic predictions in both groups, opening prospects for revisiting reciprocal recurrent selection schemes.

Incidence and mortality trends and geographic patterns of follicular lymphoma in Canada.

Background: Follicular lymphoma (fl) is the most common indolent lymphoma and the 2nd most common non-Hodgkin lymphoma, accounting for 10%-20% of all lymphomas in the Western world. Epidemiologic and geographic trends of fl in Canada have not been investigated. Our study's objective was to analyze incidence and mortality rates and the geographic distribution of fl patients in Canada for 1992-2010. Methods: Demographic and geographic patient data for fl cases were obtained using the Canadian Cancer Registry, the Registre québécois du cancer, and the Canadian Vital Statistics database. Incidence and mortality rates and 95% confidence intervals were calculated per year and per geographic area. Rates were plotted using linear regression models to assess trends over time. Overall data were mapped using Microsoft Excel mapping software (Redmond, WA, U.S.A.) to identify case clusters across Canada. Results: Approximately 22,625 patients were diagnosed with fl during 1992-2010. The age-standardized incidence rate of this malignancy in Canada was 38.3 cases per million individuals per year. Geographic analysis demonstrated that a number of Maritime provinces and Manitoba had the highest incidence rates, and that the provinces of Nova Scotia and Quebec had the highest mortality rates in the nation. Regional data demonstrated clustering of fl within cities or regions with high herbicide use, primary mining, and a strong manufacturing presence. Conclusions: Our study provides a comprehensive overview of the fl burden and its geographic distribution in Canada. Regional clustering of this disease in concentrated industrial zones strongly suggests that multiple environmental factors might play a crucial role in the development of this lymphoma.

[Second- or third-line treatment with erlotinib in EGFR wild-type non-small cell lung cancer: Real-life data]. / Erlotinib en 2e ou 3e ligne pour les cancers bronchiques non à petites cellules sans mutation de l'EGFR : données en vie réelle.

INTRODUCTION: The benefit of tyrosine kinase inhibitors for patients with an EGFR wild-type non-small cell lung cancer (NSCLC) remains controversial. METHODS: The survival of patients with an EGFR wild-type NSCLC who received second- or third-line erlotinib treatment was assessed using real-life data that had been collected in a prospective, national, multicenter, non-interventional cohort study. RESULTS: Data from 274 patients were analysed, 185 (68%) treated with erlotinib and 89 (32%) treated with supportive care only. The median overall survival was 4.2months (95% CI [3.5; 5.4]) with erlotinib, and 1.3months (95% CI [1.0; 1.8]) with supportive care. Survival rate at 3, 6, and 12months was 62%, 37%, and 17%, respectively, with erlotinib, versus 20%, 8%, et 3%, with exclusive supportive care. Significant predictive factors for longer overall survival were the presence of adenocarcinoma, and use of 1st line chemotherapy including either taxanes, pemetrexed or vinorelbine (P<0.05). CONCLUSION: Erlotinib remains a valuable therapeutic option to treat inoperable locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen in fragile patients who are not eligible for chemotherapy.

Evidence for Weakly Correlated Oxygen Holes in the Highest-T_{c} Cuprate Superconductor HgBa_{2}Ca_{2}Cu_{3}O_{8+δ}.

We study the electronic structure of HgBa_{2}Ca_{2}Cu_{3}O_{8+δ} (Hg1223; T_{c}=134 K) using photoemission spectroscopy (PES) and x-ray absorption spectroscopy (XAS). Resonant valence band PES across the O K edge and Cu L edge identifies correlation satellites originating in O 2p and Cu 3d two-hole final states, respectively. Analyses using the experimental O 2p and Cu 3d partial density of states show quantitatively different on-site Coulomb energy for the Cu site (U_{dd}=6.5±0.5 eV) and O site (U_{pp}=1.0±0.5 eV). Cu_{2}O_{7}-cluster calculations with nonlocal screening explain the Cu 2p core level PES and Cu L-edge XAS spectra, confirm the U_{dd} and U_{pp} values, and provide evidence for the Zhang-Rice singlet state in Hg1223. In contrast to other hole-doped cuprates and 3d-transition metal oxides, the present results indicate weakly correlated oxygen holes in Hg1223.

Predicting genomic selection efficiency to optimize calibration set and to assess prediction accuracy in highly structured populations.

KEY MESSAGE: We propose a criterion to predict genomic selection efficiency for structured populations. This criterion is useful to define optimal calibration set and to estimate prediction reliability for multiparental populations. Genomic selection refers to the use of genotypic information for predicting the performance of selection candidates. It has been shown that prediction accuracy depends on various parameters including the composition of the calibration set (CS). Assessing the level of accuracy of a given prediction scenario is of highest importance because it can be used to optimize CS sampling before collecting phenotypes, and once the breeding values are predicted it informs the breeders about the reliability of these predictions. Different criteria were proposed to optimize CS sampling in highly diverse panels, which can be useful to screen collections of genotypes. But plant breeders often work on structured material such as biparental or multiparental populations, for which these criteria are less adapted. We derived from the generalized coefficient of determination (CD) theory different criteria to optimize CS sampling and to assess the reliability associated to predictions in structured populations. These criteria were evaluated on two nested association mapping (NAM) populations and two highly diverse panels of maize. They were efficient to sample optimized CS in most situations. They could also estimate at least partly the reliability associated to predictions between NAM families, but they could not estimate differences in the reliability associated to the predictions of NAM families using the highly diverse panels as calibration sets. We illustrated that the CD criteria could be adapted to various prediction scenarios including inter and intra-family predictions, resulting in higher prediction accuracies.

Patients' preference of trastuzumab administration (subcutaneous versus intravenous) in HER2-positive metastatic breast cancer: Results of the randomised MetaspHer study.

HannaH (NCT00950300) and PrefHer (NCT01401166) studies validated the subcutaneous (H-s.c.) formulation of trastuzumab as effective and safe as intravenous (H-i.v.) and highly preferred by patients in early breast cancer. The present randomised MetaspHer trial (NCT01810393) is the first study assessing patient's preference in metastatic setting. METHODS: Patients with HER2-positive metastatic breast cancer who completed a first line chemotherapy with trastuzumab and achieved a long-term response lasting more than 3 years were randomised to receive 3 cycles of 600-mg fixed-dose adjuvant H-s.c., followed by 3 cycles of standard H-i.v., or the reverse sequence. Primary end-point was overall preference for H-s.c. or H-i.v. at cycle six, assessed by Patient Preference Questionnaire (PPQ). Secondary end-points included healthcare professional (HCP) satisfaction; safety and tolerability; quality of life. RESULTS: Hundred and thirteen patients were randomised and treated. H-s.c. was preferred by 79/92 evaluable intent-to-treat patients (85.9%, 95% confidence interval [CI; 78.8-93.0]; p < 0.001), 13/92 preferred H-i.v. (14.1%, 95% CI [7.0-21.3]). HCPs were most satisfied with H-s.c. (56/88 available data, 63.6%, [53.6-73.7]). On the safety population, adverse events occurred in 73 (67.6%) and 49 (44.1%) patients during the H-s.c. and H-i.v. periods, respectively; 7 (6.5%) and 4 (3.6%) were grade ≥ III, 3 (2.8%) and 2 (1.8%) were serious. CONCLUSION: The safety was consistent with the known H-i.v. and H-s.c. profiles without safety concern raised. Definitively, patients preferred H-s.c. as reported in early stage by PrefHer study.

Pazopanib or placebo in completely resected stage I NSCLC patients: results of the phase II IFCT-0703 trial.

BACKGROUND: Adjuvant treatment in resected stage I non-small-cell lung cancer (NSCLC) is generally not recommended. Pazopanib is an oral tyrosine kinase inhibitor of VEGFR-1/2/3 and PDGFR-α/ß. We explored the feasibility and efficacy of adjuvant pazopanib in this population. PATIENTS AND METHODS: In this double-blind phase II/III trial, patients with resected stage I NSCLC were randomized to placebo or pazopanib 800 mg/day (P800) for 6 months with a two-step Fleming design. The primary endpoint was compliance (percentage of patients receiving ≥3 months pazopanib). From the interim analysis after 64 patients were included, the IDMC recommended reducing to pazopanib 400 mg/day (P400) due to insufficient compliance, with a one-step Fleming. Although unplanned, survival data were analyzed. RESULTS: A total of 71 patients were enrolled in each arm; 61% were male, 91% were smokers, median age was 60 years, 80% had pathological stage IA, and 16% had squamous cell carcinoma. Pazopanib compliance was 38% [95% confidence interval (CI) 23-55] with P800, increasing to 69% (95% CI 50-84; P = 0.027) with P400. Two patients had grade 4 toxicities with P800. The most common grade 3 toxicities were increased transaminases (16%), hypertension (13%), and diarrhea (9%) with P800, and gastrointestinal disorders (16%; 6% diarrhea) and hypertension (6%) with P400. Median follow-up was 47 months. Three-year recurrence-free survival was 76% (95% CI 65%-86%) with pazopanib and 83% (95% CI 74%-92%) with placebo [hazard ratio = 1.3 (95% CI 0.6-2.7), P = 0.53]. Five-year overall survival was 83% (95% CI 72-94) with pazopanib and 94% [95% CI 88-100] with placebo [hazard ratio = 1.8 (95% CI 0.6-5.5), P = 0.26]. CONCLUSIONS: In resected stage I NSCLC patients adjuvant 400 mg/day pazopanib but not 800 mg/day was feasible, although possibly infra-therapeutic and failed to improve relapse-free survival.

General and specific combining abilities in a maize (Zea mays L.) test-cross hybrid panel: relative importance of population structure and genetic divergence between parents.

KEY MESSAGE: General and specific combining abilities of maize hybrids between 288 inbred lines and three tester lines were highly related to population structure and genetic distance inferred from SNP data. Many studies have attempted to provide reliable and quick methods to identify promising parental lines and combinations in hybrid breeding programs. Since the 1950s, maize germplasm has been organized into heterotic groups to facilitate the exploitation of heterosis. Molecular markers have proven efficient tools to address the organization of genetic diversity and the relationship between lines or populations. The aim of the present work was to investigate to what extent marker-based evaluations of population structure and genetic distance may account for general (GCA) and specific (SCA) combining ability components in a population composed of 800 inter and intra-heterotic group hybrids obtained by crossing 288 inbred lines and three testers. Our results illustrate a strong effect of groups identified by population structure analysis on both GCA and SCA components. Including genetic distance between parental lines of hybrids in the model leads to a significant decrease of SCA variance component and an increase in GCA variance component for all the traits. The latter suggests that this approach can be efficient to better estimate the potential combining ability of inbred lines when crossed with unrelated lines, and limits the consequences of tester choice. Significant residual GCA and SCA variance components of models taking into account structure and/or genetic distance highlight the variation available for breeding programs within structure groups.

Dent and Flint maize diversity panels reveal important genetic potential for increasing biomass production.

KEY MESSAGE: Genetic and phenotypic analysis of two complementary maize panels revealed an important variation for biomass yield. Flowering and biomass QTL were discovered by association mapping in both panels. The high whole plant biomass productivity of maize makes it a potential source of energy in animal feeding and biofuel production. The variability and the genetic determinism of traits related to biomass are poorly known. We analyzed two highly diverse panels of Dent and Flint lines representing complementary heterotic groups for Northern Europe. They were genotyped with the 50 k SNP-array and phenotyped as hybrids (crossed to a tester of the complementary pool) in a western European field trial network for traits related to flowering time, plant height, and biomass. The molecular information revealed to be a powerful tool for discovering different levels of structure and relatedness in both panels. This study revealed important variation and potential genetic progress for biomass production, even at constant precocity. Association mapping was run by combining genotypes and phenotypes in a mixed model with a random polygenic effect. This permitted the detection of significant associations, confirming height and flowering time quantitative trait loci (QTL) found in literature. Biomass yield QTL were detected in both panels but were unstable across the environments. Alternative kinship estimator only based on markers unlinked to the tested SNP increased the number of significant associations by around 40% with a satisfying control of the false positive rate. This study gave insights into the variability and the genetic architectures of biomass-related traits in Flint and Dent lines and suggests important potential of these two pools for breeding high biomass yielding hybrid varieties.

Maximizing the reliability of genomic selection by optimizing the calibration set of reference individuals: comparison of methods in two diverse groups of maize inbreds (Zea mays L.).

Genomic selection refers to the use of genotypic information for predicting breeding values of selection candidates. A prediction formula is calibrated with the genotypes and phenotypes of reference individuals constituting the calibration set. The size and the composition of this set are essential parameters affecting the prediction reliabilities. The objective of this study was to maximize reliabilities by optimizing the calibration set. Different criteria based on the diversity or on the prediction error variance (PEV) derived from the realized additive relationship matrix-best linear unbiased predictions model (RA-BLUP) were used to select the reference individuals. For the latter, we considered the mean of the PEV of the contrasts between each selection candidate and the mean of the population (PEVmean) and the mean of the expected reliabilities of the same contrasts (CDmean). These criteria were tested with phenotypic data collected on two diversity panels of maize (Zea mays L.) genotyped with a 50k SNPs array. In the two panels, samples chosen based on CDmean gave higher reliabilities than random samples for various calibration set sizes. CDmean also appeared superior to PEVmean, which can be explained by the fact that it takes into account the reduction of variance due to the relatedness between individuals. Selected samples were close to optimality for a wide range of trait heritabilities, which suggests that the strategy presented here can efficiently sample subsets in panels of inbred lines. A script to optimize reference samples based on CDmean is available on request.

Diversity and linkage disequilibrium features in a composite public/private dent maize panel: consequences for association genetics as evaluated from a case study using flowering time.

Recent progress in genotyping and resequencing techniques have opened new opportunities for deciphering quantitative trait variation by looking for associations between traits of interest and polymorphisms in panels of diverse inbred lines. Association mapping raises specific issues related to the choice of appropriate (i) panels and marker-densities and (ii) statistical methods to capture associations. In this study, we used a panel of 314 maize inbred lines from the dent pool, composed of inbred material from public institutes (113 inbred lines) and a private company (201 inbred lines). We showed that local LD was higher and genetic diversity lower in the material of private origin than in the public material. We compared the results obtained by different software for identifying population structure and computing relatedness among lines, and ran association tests for earliness related traits. Our results confirmed the importance of the mite polymorphism of Vgt1 on flowering time, but also showed that its effect can be captured by zmRap2.7 polymorphisms located 70 kb apart. We also highlighted associations with polymorphisms within genes putatively involved in lignin biosynthesis pathway, which deserve further investigations.

The genetic basis of heterosis: multiparental quantitative trait loci mapping reveals contrasted levels of apparent overdominance among traits of agronomical interest in maize (Zea mays L.).

Understanding the genetic bases underlying heterosis is a major issue in maize (Zea mays L.). We extended the North Carolina design III (NCIII) by using three populations of recombinant inbred lines derived from three parental lines belonging to different heterotic pools, crossed with each parental line to obtain nine families of hybrids. A total of 1253 hybrids were evaluated for grain moisture, silking date, plant height, and grain yield. Quantitative trait loci (QTL) mapping was carried out on the six families obtained from crosses to parental lines following the "classical" NCIII method and with a multiparental connected model on the global design, adding the three families obtained from crosses to the nonparental line. Results of the QTL detection highlighted that most of the QTL detected for grain yield displayed apparent overdominance effects and limited differences between heterozygous genotypes, whereas for grain moisture predominance of additive effects was observed. For plant height and silking date results were intermediate. Except for grain yield, most of the QTL identified showed significant additive-by-additive epistatic interactions. High correlation observed between heterosis and the heterozygosity of hybrids at markers confirms the complex genetic basis and the role of dominance in heterosis. An important proportion of QTL detected were located close to the centromeres. We hypothesized that the lower recombination in these regions favors the detection of (i) linked QTL in repulsion phase, leading to apparent overdominance for heterotic traits and (ii) linked QTL in coupling phase, reinforcing apparent additive effects of linked QTL for the other traits.

Long-term follow-up of HER2-overexpressing stage II or III breast cancer treated by anthracycline-free neoadjuvant chemotherapy.

BACKGROUND: Very effective trastuzumab-based primary systemic therapy (PST) can be proposed for conservative surgery purpose to human epidermal growth factor receptor 2 (HER2)-positive breast cancer (HER2+BC). Long-term follow-up (LTFU) warrants further data. PATIENTS AND METHODS: LTFU of patients, with stage II/III HER2+BC, treated by trastuzumab associated with docetaxel (Taxotere(®)) and/or carboplatin used as anthracycline-free PST was studied. RESULTS: Among 135 patients, with a median follow-up of 48.3 months [95% confidence interval (CI) 45.3-52.4 months], the relapse-free survival (RFS) rate was 73.2% (95% CI 63.76% to 80.55%) while the overall survival (OS) rate was 91.87% (95% CI 84.23% to 95.90%). Adjuvant trastuzumab favorably influenced RFS in univariate analysis while the pathological nodal invasion unfavorably influenced RFS [Cox multivariate analysis (hazard ratio = 2.80, 95% CI 1.36-5.76, P = 0.0052)] and OS. Cardiac toxicity was minor (2.2% transient, reversible asymptomatic decrease in left ventricular ejection fraction). CONCLUSION: This is the first report of LTFU showing that anthracycline-free trastuzumab-based PST combined either with docetaxel and/or carboplatin can achieve, without cardiac toxicity, very competitive results in terms of pathological complete response, RFS and OS, in HER2+BC. The choice of this schedule could be proposed to patients with vascular contraindication for anthracyclines or because patient's or physician's preference for a taxane-only schedule.